Many of the big, outstanding problems in biology involve complex, highly interactive processes. Nowhere is this more true than in the field of human health where disease severity can depend on social climate, individual behavior and previous exposures. Because of advances in biotechnology, it is now possible to investigate complex biological processes to a level of quantitative and functional detail unimaginable 20 or 30 years ago. However, the task is greatly complicated by the fact that the processes themselves cut across traditional scientific disciplines, leaving few specialized researchers fully prepared to answer them alone. There is clearly a great need for interdisciplinary research. What is less clear is how to achieve this at a level commensurate with the complexity of the problems we face. Central to our solution to this challenge is the Modeling Core. The Modeling Core is a research space, an arrangement of researchers around a nucleus of core fellows, and a culture of intellectual exchange all geared toward solving complex problems. The focus of the Modeling Core will initially be the projects of this center, each of which investigates complex interactions that underlie viral co- infection. With time, the core will expand to include new investigators tackling new biomedical problems, developing new methodological approaches to address them, and benefiting from the interdisciplinary dynamics within the core. We will achieve this vision through realizing the following aims: 1) establish the core: the people, its research space, the culture, and a strategy for assessment, 2) engage in integrative modeling that supports individual research projects and 3) promote outreach by extending core services and developing workshops. Interdisciplinary research addresses complex problems spanning multiple levels of biological organization, and it requires a deep exchange of ideas among fields to generate genuine insights. The Modeling Core is an innovative way to power interdisciplinary research by distilling the three critical features of this exchange: a shared language for connecting, a space for interaction, and a diversity of participants.